西加韦单抗和替沙格韦单抗作为疫苗无应答者肾移植受者在 SARS-CoV-2 BA.2 和 BA.4/5 变异株流行期间的暴露前预防-一项前瞻性队列研究（RESCUE-TX）。

Cilgavimab and tixagevimab as pre-exposure prophylaxis in vaccine non-responder kidney transplant recipients during a period of prevalent SARS-CoV-2 BA.2 and BA.4/5 variants-a prospective cohort study (RESCUE-TX).

机构信息

Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Department of Laboratory Medicine, Division of Clinical Virology, Medical University of Vienna, Vienna, Austria.

出版信息

EBioMedicine. 2024 Nov;109:105417. doi: 10.1016/j.ebiom.2024.105417. Epub 2024 Oct 22.

BACKGROUND

The response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination is severely impaired in patients on maintenance immunosuppression after kidney transplantation.

METHODS

We conducted a prospective cohort study of 194 kidney transplant recipients (KTR) who exhibited no response to SARS-CoV-2 vaccinations (i.e., SARS-CoV-2 spike protein antibodies ≤264 U/mL) and had no prior documented infection. Patients received 300 mg of cilgavimab/tixagevimab as SARS-CoV-2 pre-exposure prophylaxis (PrEP) between March 4, 2022, and May 3, 2022 and were contrasted to a matched cohort of 186 KTRs also without immunization again defined as SARS-CoV-2 spike protein antibodies ≤264 U/mL and no documented prior infection. The primary outcome was the serum kinetics of cilgavimab/tixagevimab, the secondary endpoints were time to SARS-CoV-2 breakthrough infection, severity of disease and variant specific live viral in vitro neutralization tests of patient sera.

FINDINGS

Longitudinal serum level monitoring showed a half-life of 91 days for both antibodies (95% CI 86-95 days for cilgavimab and 85-96 days for tixagevimab) in KTRs. In vitro neutralization tests showed effectiveness against the BA.2 omicron subvariant but not BA.5. The cumulative incidence of SARS-CoV-2 infections until May 15, 2022, (BA.2 dominance) was 15/194 vs 36/186 in the PrEP and control group respectively (OR = 0.35, 95% CI 0.18-0.66) but was not different thereafter (BA.4/5 dominance). The number of severe infections during the BA.2 period was lower in the prophylaxis than in the control group (OR = 0.37, 95% CI 0.17-0.79).

INTERPRETATION

This study showed that SARS-CoV-2 PrEP with cilgavimab/tixagevimab demonstrated clinical effectiveness against variants that are neutralised (BA.2) but not against BA.4/5.

FUNDING

This study was funded by the Medical University of Vienna and an unrestricted grant from AstraZeneca (ESR-21-21585).

背景

在接受维持性免疫抑制治疗的肾移植患者中，严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）疫苗的反应严重受损。

方法

我们对 194 名肾移植受者（KTR）进行了一项前瞻性队列研究，这些受者在接种 SARS-CoV-2 疫苗后没有产生反应（即 SARS-CoV-2 刺突蛋白抗体≤264 U/mL），并且没有先前记录的感染。患者在 2022 年 3 月 4 日至 2022 年 5 月 3 日期间接受了 300mg 的 cilgavimab/tixagevimab 作为 SARS-CoV-2 暴露前预防（PrEP），并与 186 名未接受免疫接种的 KTR 相匹配，也定义为 SARS-CoV-2 刺突蛋白抗体≤264 U/mL，且无先前感染的记录。主要结局是 cilgavimab/tixagevimab 的血清动力学，次要结局是 SARS-CoV-2 突破性感染的时间、疾病严重程度和患者血清的变异特异性活病毒体外中和试验。

发现

KTR 中两种抗体的半衰期分别为 91 天（95%CI 86-95 天为 cilgavimab，85-96 天为 tixagevimab）。体外中和试验表明对 BA.2 奥密克戎亚变种有效，但对 BA.5 无效。截至 2022 年 5 月 15 日，PrEP 组和对照组的 SARS-CoV-2 感染累积发生率分别为 15/194 和 36/186（OR=0.35，95%CI 0.18-0.66），但此后无差异（BA.4/5 优势）。在 BA.2 期间，预防组的严重感染人数低于对照组（OR=0.37，95%CI 0.17-0.79）。